High refractive index aromatic-based prepolymers

ABSTRACT

Relatively high refractive index polymeric compositions and ophthalmic devices such as for example intraocular lenses and corneal inlays made therefrom are described herein. The preferred polymeric compositions are produced through the copolymerization of one or more aromatic-substituted polysiloxane prepolymers with one or more aromatic monomers, alkylated monomers or hydrophilic monomers.

FIELD OF THE INVENTION

[0001] The present invention relates to prepolymers useful in themanufacture of biocompatible medical devices. More particularly, thepresent invention relates to aromatic-substituted polysiloxaneprepolymers capable of copolymerization with one or more other monomersto form polymeric compositions having desirable physical characteristicsand refractive indices for use in the manufacture of ophthalmicimplants.

BACKGROUND OF THE INVENTION

[0002] Since the 1940's optical devices in the form of intraocular lens(IOL) implants have been utilized as replacements for diseased ordamaged natural ocular lenses. In most cases, an intraocular lens isimplanted within an eye at the time of surgically removing the diseasedor damaged natural lens, such as for example, in the case of cataracts.For decades, the preferred material for fabricating such intraocularlens implants was poly(methyl methacrylate), which is a rigid, glassypolymer.

[0003] Softer, more flexible IOL implants have gained in popularity inmore recent years due to their ability to be compressed, folded, rolledor otherwise deformed. Such softer IOL implants may be deformed prior toinsertion thereof through an incision in the cornea of an eye. Followinginsertion of the IOL in an eye, the IOL returns to its originalpre-deformed shape due to the memory characteristics of the softmaterial. Softer, more flexible IOL implants as just described may beimplanted into an eye through an incision that is much smaller, i.e.,less than 4.0 mm, than that necessary for more rigid IOLs, i.e., 5.5 to7.0 mm. A larger incision is necessary for more rigid IOL implantsbecause the lens must be inserted through an incision in the corneaslightly larger than the diameter of the inflexible IOL optic portion.Accordingly, more rigid IOL implants have become less popular in themarket since larger incisions have been found to be associated with anincreased incidence of postoperative complications, such as inducedastigmatism.

[0004] With recent advances in small-incision cataract surgery,increased emphasis has been placed on developing soft, foldablematerials suitable for use in artificial IOL implants. In general, thematerials of current commercial IOLs fall into one of three categories:silicones, hydrophilic acrylics and hydrophobic acrylics.

[0005] In general, high water content hydrophilic acrylics, or“hydrogels,” have relatively low refractive indices, making them lessdesirable than other materials with respect to minimal incision size.Low refractive index materials require a thicker IOL optic portion toachieve a given refractive power. Silicone materials may have higherrefractive indices than high-water content hydrogels, but tend to unfoldexplosively after being placed in the eye in a folded position.Explosive unfolding can potentially damage the corneal endotheliumand/or rupture the natural lens capsule and associated zonules. Lowglass transition temperature hydrophobic acrylic materials are desirablebecause they typically have a high refractive index and unfold moreslowly and more controllably than silicone materials. Unfortunately, lowglass transition temperature hydrophobic acrylic materials, whichcontain little or no water initially, may absorb pockets of water invivo causing light reflections or “glistenings.” Furthermore, it may bedifficult to achieve ideal folding and unfolding characteristics due tothe temperature sensitivity of some acrylic polymers.

[0006] Because of the noted shortcomings of current polymeric materialsavailable for use in the manufacture of ophthalmic devices, there is aneed for stable, biocompatible polymeric materials having desirablephysical characteristics and refractive indices.

SUMMARY OF THE INVENTION

[0007] Soft, foldable, high refractive index, high elongation, polymericcompositions of the present invention are synthesized through thecopolymerization of aromatic-substituted polysiloxane prepolymers withone or more aromatic monomers, alkyl monomers, hydrophilic monomers or acombination thereof. Production processes of the present invention usingthe subject aromatic-substituted polysiloxane prepolymers, producematerials having desirable physical properties for use in themanufacture of ophthalmic devices. The polymeric compositions of thepresent invention are transparent and have relatively high strength fordurability during surgical manipulation, relatively high elongation andrelatively high refractive index. The subject polymeric compositions areparticularly well suited for use in the manufacture of ophthalmicdevices such as intraocular lens (IOL) implants, contact lenses,keratoprostheses, corneal rings, corneal inlays and the like.

[0008] Preferred aromatic-substituted polysiloxane prepolymers for usein the production of the polymeric compositions of present inventionhave a structure generally represented by Formula 1 below, which may beproduced from precursors having a structure generally represented byFormula 2 below:

[0009] wherein the V groups may be the same or different unsaturatedphoto or thermal polymerizable substituents of the general structureR₃CH═C(R₄)(CH₂)_(p)(W)_(q)(Z)_(q)(Ar)_(q)R₅; the R groups may be thesame or different saturated C₁₋₁₀ hydrocarbon substituents; the R₁groups may be the same or different alkyl substituents; the R₂ groupsmay be the same or different alkyl substituents, fluoroalkylsubstituents or alkyl-fluoroalkyl substituents with ether linkagestherebetween, or the same or different aromatic substituents; the Lgroups, which may or may not be present in the subject prepolymers, maybe the same or different urethane, urea, carbonate or ester linkages; yis a natural number greater than 4 representing the sum of siloxanemoieties with randomly differing R₂ groups as defined above with a molarratio of aromatic substituents to alkyl substituents no less than 1:4; xis a natural number such that the prepolymer molecular weight is atleast approximately 1000 and refractive index is at least approximately1.45 or greater; m is a natural number greater than 4 representing thesum of siloxane moieties with randomly differing R₂ groups as definedabove with a molar ratio of aromatic substituents to alkyl substituentsno less than 1:4 such that the prepolymer molecular weight is at leastapproximately 1000 and refractive index is at least approximately 1.45or greater; R₃ is selected from the group consisting of hydrogen, C₁₋₁₀alkyl and —CO—U—R₁; R₄ is selected from the group consisting of hydrogenand methyl; R₅ is a C₁₋₁₀ divalent alkylene radical; the W group isselected from the group consisting of —CO— and —OCO—; the Z group isselected from the group consisting of —O— and —NH—; the Z₁ groups may bethe same or different selected from the group consisting of —OH and—NH₂; the Ar groups may be the same or different C₆-30 aromaticradicals; p is a non-negative integer less than 7; q is either 0 or 1;and U is selected from the group consisting of —OC₁₋₁₂ alkyl radical,—SC₁₋₁₂ alkyl radical and —NHC₁₋₁₂ alkyl radical.

[0010] Accordingly, it is an object of the present invention to providetransparent, biocompatible polymeric compositions having desirablephysical characteristics and relatively high refractive indices.

[0011] Another object of the present invention is to provide polymericcompositions having relatively high refractive indices and good clarity.

[0012] Another object of the present invention is to provide polymericcompositions suitable for use in the manufacture of ophthalmic devices.

[0013] Another object of the present invention is to provide polymericcompositions suitable for use in the manufacture of intraocular lensimplants.

[0014] Still another object of the present invention is to providepolymeric compositions that are economical to produce.

[0015] These and other objectives and advantages of the presentinvention, some of which are specifically described and others that arenot, will become apparent from the detailed description and claims thatfollow.

DETAILED DESCRIPTION OF THE INVENTION

[0016] The present invention relates to novel aromatic-substitutedpolysiloxane prepolymers and the use of such prepolymers to producebiocompatible polymeric compositions having desirable physicalproperties and relatively high refractive indices for use in themanufacture of ophthalmic devices. The aromatic-substituted polysiloxaneprepolymers of the present invention are represented generally byFormula 1 below which are produced from precursors represented generallyby Formula 2 below:

[0017] wherein the V groups may be the same or different unsaturatedphoto or thermal polymerizable substituents of the general structureR₃CH═C(R₄)(CH₂)_(p)(W)_(q)(Z)_(q)(Ar)_(q)R₅; the R groups may be thesame or different saturated C₁₋₁₀ hydrocarbon substituents such as forexample but not limited to methyl, propyl, octyl, trimethylene ortetramethylene but preferably methyl for increased stability; the R₁groups may be the same or different C₁₋₁₀ alkyl substituents such as forexample but not limited to methyl, propyl, or octyl but preferablymethyl for increased stability; the R₂ groups may be the same ordifferent selected from the group consisting of C₁₋₁₀ alkyl substituentssuch as for example but not limited to methyl, propyl or octyl butpreferably methyl for increased stability, C₁₋₁₀fluoroalkyl substituentssuch as for example but not limited to fluoromethyl, fluoropropyl orfluorooctyl but preferably fluoromethyl for increased stability, C₂₋₂₀alkyl-fluoroalkyl substituents, which may or may not have ether linkagesbetween the alkyl and fluoroalkyl substituents, such as for example butnot limited to methyl-fluoromethyl, propyl-fluorobutyl oroctyl-fluoropentyl but preferably methyl-fluoromethyl for increasedstability, and C₆₋₃₀ aromatic substituents such as for example but notlimited to phenyl or naphthyl; the L groups, which may or may not bepresent in the subject prepolymers, may be the same or differenturethane, urea, carbonate or ester linkages such as for example but notlimited to T, T-R₆-T or T-R₆-T-R₇-T-R₆-T; y is a natural number greaterthan 4 representing the sum of siloxane moieties with randomly differingR₂ groups as defined above so as to have a molar ratio of aromaticsubstituents to alkyl substituents no less than 1:4; x is a naturalnumber such that the prepolymer molecular weight is at leastapproximately 1000 and refractive index is at least approximately 1.45;m is a natural number greater than 4 representing the sum of siloxanemoieties with randomly differing R₂ groups as defined above with a molarratio of aromatic substituents to alkyl substituents no less than 1:4such that the prepolymer molecular weight is at least approximately 1000and refractive index is at least approximately 1.45 or greater; R₃ isselected from the group consisting of hydrogen, C₁₋₁₀ alkyl such as forexample but not limited to methyl, propyl or octyl and —CO—U—R₁, butpreferably hydrogen; R₄ is selected from the group consisting ofhydrogen and methyl; R₅ is a C₁₋₁₀ divalent alkylene radical such as forexample but not limited to methylene or butylene but preferablymethylene; the W group is selected from the group consisting of —CO— and—OCO—; the Z group is selected from the group consisting of —O— and—NH—; the Z₁ groups may be the same or different selected from the groupconsisting of —OH and —NH₂; the Ar groups may be the same or differentC₆₋₃₀ aromatic radicals such as for example but not limited to radicalsof benzene, naphthalene or phenanthrene; p is a non-negative integerless than 7; q is either 0 or 1; the T groups may be the same ordifferent selected from the group consisting of —OCONH—, —NHCOO—,—NHCONH—, —OCOO—, —OCO— and —COO—; R₆ is a residue of diisocyanate afterremoving isocyanate groups; R₇ is a residue of diol after removing —OHgroups; and U is selected from the group consisting of —OC₁₋₁₂ alkylradical, —SC₁₋₁₂ alkyl radical and —NHC₁₋₁₂ alkyl radical.

[0018] Many α,ω-bis-hydroxyalkyl polysiloxanes or α,ω-bis-aminoalkylpolysiloxanes with varying numbers of aromatic units such as thoserepresented by the structure of Formula 2 are useful in makingprepolymers of the present invention. The desired number of aromaticunits, such as for example phenyl groups, and the desired prepolymermolecular weight can be produced by reacting 1,3-bis-hydroxyalkyltetramethyldisiloxane or 1,3-bis-aminoalkyl tetramethyldisiloxane withdifferent combinations of dimethyldimethoxysilane,diphenydimethoxysilane and methylphenyldimethoxysilane at molar ratiosof choice. Alternatively, the same prepolymers may be prepared by thesame method using cyclic siloxanes with different levels of phenylgroups, such as 1,3,5-trimethyl-1,3,5-triphenylcyclotrisiloxane,1,1,3,3,5,5-hexamethylcyclotrisiloxane,1,1,3,3,5,5-hexaphenylcyclotrisiloxane, rather than using silanes asmentioned above. Some examples of polysiloxane precursors so prepared,not intended to be limiting, areα,ω-bis-hydroxybutylpoly(methylphenylsiloxane) (HBPMPS) represented byFormula 3 below,

[0019] wherein the Ph groups may be the same or different C₀ aromaticsubstituents such as for example but not limited to phenyl; and x is thesame as that defined above for Formula 1; andα,ω-bis-hydroxybutylpoly(methylphenylsiloxane-co-dimethylsiloxane)(HBPMPS-co-DMS) represented by Formula 4 below,

[0020] wherein the Ph groups and x are the same as defined above forFormula 3.

[0021] Prepolymers of the present invention are also produced usinghydroxyalkyl-terminated polysiloxane precursors with aromatic units suchas for example HBPMPS of Formula 3 above. One example of suchprepolymers, not intended to be limiting, is derived from isophoronediisocyanate and α,ω-bis-hydroxybutylpoly(methylphenylsiloxane)(HBPMPS), end-capped with 2-hydroxyethylmethacylate as represented byFormula 5 below,

[0022] wherein IPDI represents the residue after removing the isocyanategroup, and the Ph groups and x are the same as defined above for Formula3. The prepolymer represented by Formula 5 has three blocks of IPDI andtwo blocks of HBPMPS repeating units, commonly referred to as a“diblock” prepolymer. Other prepolymers of similar structure can beprepared by the same method using a hydroxyalkyl-terminated polysiloxanewith aromatic units having a molecular weight of choice, and adiisocyanate, a diacid chloride or phosgene in a selected molar ratioand end-capped with a hydroxy or amino containing monomer such as forexample 2-hydroxyethyl methacrylate.

[0023] Soft, foldable, relatively high refractive index of approximately1.45 or greater, relatively high elongation of approximately 100 percentor greater polymeric compositions of the present invention aresynthesized through the copolymerization of one or more of the subjectaromatic-substituted polysiloxane prepolymers with one or more aromaticmonomers, alkyl monomers, hydrophilic monomers or a combination thereof.

[0024] Examples of aromatic monomers useful in the production ofpolymeric compositions of the present invention include for example butare not limited to acrylate, methacrylate, acrylamide andmethacrylamide, each with C₆₋₃₀ aromatic substituents. More specificexamples of such aromatic monomers include but are not limited to phenylacrylate, phenyl(meth)acrylate, phenyl acrylamide, benzyl acrylate,benzyl acrylamide, phenylethylacrylate, phenyl(meth)acrylamide,phenylethyl(meth)acrylate and benzyl(meth)acrylate.

[0025] Examples of alkyl monomers useful in the production of polymericcompositions of the present invention include for example but are notlimited to C₁₋₂₀ alkyl acrylate, C₁₋₂₀ alkyl methacrylate, C₅₋₂₀acrylamide and C₅₋₂₀ methacrylamide. More specific examples of suchalkyl monomers include for example but are not limited to methylacrylate, ethyl acrylate, n-propyl acrylate, n-butyl acrylate, n-hexylacrylate, n-octyl acrylate, 2-ethylhexyl acrylate, n-propylmethacrylate, n-butyl methacrylate, n-hexyl methacrylate, n-octylmethacrylate, 2-ethylhexyl methacrylate and n-octyl acrylamide.

[0026] Examples of hydrophilic monomers useful in the production ofpolymeric compositions of the present invention include for example butare not limited to N,N-dimethyl acrylamide, N-vinylpyrrolidone,2-hydroxyethyl methacrylate (HEMA), glycerol methacrylate,2-hydroxyethyl acrylate, acrylamide, n-methyl acrylamide, acrylic acidand (meth)acrylic acid.

[0027] The polymeric compositions of the present invention haverelatively high refractive indexes of approximately 1.45 or greater,relatively low glass transition temperatures of approximately 30 degreesCelsius or less and relatively high elongation of approximately 100percent or greater. The polymeric compositions of the present inventionwith the desirable physical properties noted herein are particularlyuseful in the manufacture of ophthalmic devices such as but not limitedto intraocular lenses (IOLs) and corneal inlays. Examples of polymericcompositions having the above mentioned physical characteristics includethose derived from the prepolymer of Formula 5, benzyl acrylate, benzylmethacrylate and dimethylacrylamide (DMA) at different weight ratios.These polymeric materials are either xerogels or hydrogels with up totwenty percent water content by weight per volume (W/V).

[0028] IOLs having thin optic portions are critical in enabling asurgeon to minimize surgical incision size. Keeping the surgicalincision size to a minimum reduces intraoperative trauma andpostoperative complications. A thin IOL optic portion is also criticalfor accommodating certain anatomical locations in the eye such as theanterior chamber and the ciliary sulcus. IOLs may be placed in theanterior chamber for increasing visual acuity in both aphakic and phakiceyes and placed in the ciliary sulcus for increasing visual acuity inphakic eyes.

[0029] The preferred polymeric compositions of the present inventionhave the flexibility required to allow ophthalmic devices manufacturedfrom the same to be folded or deformed for insertion into an eye throughthe smallest possible surgical incision, i.e., 3.5 mm or smaller. It isunexpected that the subject polymeric compositions described hereincould possess the ideal physical properties disclosed herein. The idealphysical properties of the subject polymeric compositions are unexpectedbecause high refractive index monomers or copolymers typically lend topolymers that have increased crystallinity and decreased clarity, whichdoes not hold true in the case of the subject polymeric compositions.

[0030] One or more suitable ultraviolet light absorbers may optionallybe used in the manufacture of the subject compositions. Such ultravioletlight absorbers include for example but are not limited toβ-(4-benzotriazoyl-3-hydroxyphenoxy) ethyl acrylate,4-(2-acryloxyethoxy)-2-hydroxybenzophenone,4-methacryloxy-2-hydroxybenzophenone,2-(2′-methacryloxy-5′-methylphenyl)benzotriazole,2-(2′-hydroxy-5′-methacryoxyethylphenyl)-2H-benzotriazole,2-[3′-tert-butyl-2′-hydroxy-5′-(3″-methacryloyloxypropyl)phenyl]-5-chlorobenzotriazole,2-[3′-tert-butyl-5′-(3″-dimethylvinylsilylpropoxy)-2′-hydroxyphenyl]-5-methoxybenzotriazole,2-(3′-allyl-2′-hydroxy-5′-methylphenyl)benzotriazole,2-[3′-tert-butyl-2′-hydroxy-5′-(3″-methacryloyloxypropoxy)phenyl]-5-methoxybenzotriazole,and2-[3′-tert-butyl-2′-hydroxy-5′-(3″-methacryloyloxypropoxy)phenyl]-5-chlorobenzotriazolewherein β-(4-benzotriazoyl-3-hydroxyphenoxy)ethyl acrylate is thepreferred ultraviolet light absorber due to its effectiveness andavailability.

[0031] The subject compositions having refractive indices ofapproximately 1.45 or greater and elongation of 100 percent or greaterare described in still greater detail in the examples that follow.

EXAMPLE 1 Preparation of Hydroxybutyl-Terminated Copolymer ofDimethylsiloxane and Diphenylsiloxane

[0032] 1,3-bis(hydroxybutyl)tetramethyl disiloxane (33.70 g, 0.118mole), dimethyldimethoxysilane (403.18 g, 3.25 moles) anddiphenyldimethoxysilane (272.33 g, 1.08 moles) were added in a one-literround bottom flask. Water (78.29 g) and concentrated hydrochloric acid(11.9 mL) were then slowly added to the flask. The contents of the flaskwere refluxed for one hour. Methanol (253.3 mL) was distilled from thecontents. Water (160 mL) and concentrated hydrochloric acid (130 mL) wasadded to the flask. The contents of the flask were refluxed for onehour. The contents of the flask were then poured into a separatoryfunnel. The silicone layer was separated, diluted with 500 mL ether andwashed once with 250 mL water, twice with 250 mL 5-percent sodiumbicarbonate aqueous solution and twice with 250 mL water. The finalorganic layer was dried with magnesium sulfate, and then vacuum strippedat 80 degrees Celsius (0.1 mm Hg) to give the crude product. The crudeproduct was then dissolved in 50/50 cyclohexanelmethylene chloride andthen passed through a silica gel column with the same solvent mixture.The final product was collected in tetrahydrofuran (THF) by passing THFthrough the silica gel column. The THF fractions were combined, driedand vacuum stripped to give the final product. Size exclusionchromatography (SEC) measurements of the final product indicated lessthan three percent cyclics and a molecular weight of 2821 by titration.

EXAMPLE 2 Preparation of Methacylate-Capped Prepolymer of PolysiloxaneContaining Both Dimethylsiloxane and Diphenylsiloxane Units

[0033] A 500-mL round bottom flask equipped with reflux condenser andnitrogen blanket was charged with isophorone diisocyanate (5.031 g,0.0227 mole), the hydroxybutyl-terminated copolymer of dimethylsiloxaneand the diphenylsiloxane from Example 1 (51.4465 g, 0.0189 mole),dibutyltin dilaurate (0.1811 g) and methylene chloride (150 mL). Theflask contents were refluxed. After about 90 hours of reflux, theisocyanate was found decreased to 16.2 percent (theoretical 16.7percent) of original. The contents of the flask were allowed to cool toambient temperature. Hydroxyethyl methacrylate (HEMA) (1.1572 g) and1,1′-2-bi-naphthol (5.7 mg) were added to the flask and stirred. Afterseven days, NCO peak disappeared from IR spectrum and the reaction wasterminated. The product was obtained at quantitative yield afterremoving solvent.

EXAMPLE 3 Preparation of Hydroxybutyl-Terminated Polymethylsiloxane withFifty Percent Phenyl Content

[0034] 1,3-bis (hydroxybutyl)tetramethyldisiloxane (13.18 g, 0.474 mole)and dimethoxyphenylmethylsilane (238.08 g, 1.306 moles) were added to aone-liter round bottom flask. Water (23.58 g or 1.31 mole) andconcentrated hydrochloric acid (4.8 mL) were then slowly added to theflask and the contents refluxed at 70 degrees Celsius for one hour.After refluxing, methanol (69.2 g) was distilled from the flask and 44mL of water and 44 mL of concentrated hydrochloric acid were added tothe reaction mixture. The contents of the flask were then refluxed for3.5 hours prior to being poured into a separatory funnel. The siliconelayer was separated, diluted with 500-mL ether and washed twice with100-ml water, twice with 100 mL five percent sodium bicarbonate aqueoussolution and twice with 250-mL water. The final organic layer was driedwith magnesium sulfate, and then vacuum stripped at 80 degrees Celsius(0.1 mm Hg) to give a clear viscous crude product. The crude product wasthen purified by silica gel column chromatography using the same methodas described in Example 1 above. The THF solutions containing productwere combined and dried with magnesium sulfate. The solvent was vacuumstripped to give the final product. The molecular weight of the finalproduct as determined by titration was 2,697.

EXAMPLE 4 Preparation of Methacrylate-Capped Prepolymer of PolysiloxaneContaining Methylphenyl Siloxane Units

[0035] The procedure and feed ratio of components used in the presentexample were the same as those of Example 2 above, except hydroxybutylterminated polymethylphenylsilloxane was used rather thanhydroxybutyl-terminated copolymer of dimethylsiloxane anddiphenylsiloxane.

EXAMPLE 5 Preparation of Hydroxybutyl-Terminated Copolymer ofDimethylsiloxane and Diphenylsiloxane with a 27:9 Ratio of Methyl/Phenyland a Molecular Weight of 4000

[0036] The preparation procedure, ingredients and ingredient feed ratioused in the present example were the same as those of Example 1, exceptpreparative SEC was used to purify the crude product. In so doing, thecrude product was dissolved in THF (10% w/v) and passed through apreparative SEC unit. The final product, after stripping off allsolvent, was over 97 percent pure, with less than 3 percent cyclicimpurities. The molecular weight of the final product as determined bytitration was 4158.

EXAMPLE 6 Preparation of Methacrylate-Capped Prepolymer of PolysiloxaneContaining Both Dimethylsiloxane and Diphenylsiloxane with 25 PercentPhenyl Units

[0037] The procedure employed in the present example was the same asthat described in Example 2 above, except a feed ratio of 4.5:3.5:2.0 ona molar basis for isophorone diisocyanate, silicon of Example 5 and HEMAwas used. The isocyanate content before adding the HEMA was 18.5percent.

EXAMPLE 7 Preparation of Hydroxybutyl-Terminated Copolymer ofDimethylsiloxane and Phenylmethylsiloxane with a 1:3 Ratio of TotalMethyl to Phenyl Attached to Silicon and Molecular Weight of 4000

[0038] In the present example, the same procedure was employed as thatof Example 1, except that the amounts of ingredients used were varied.In the present example, 4-bis(4-hydroxybutyl)tetramethyldisiloxane(19.08 g, 0.0686 mole), dimethoxydimethylsilane (151.67 g, 1.223 mole)and dimethoxyphenylmethylsilane (222.24 g, 1.219 mole) were used. Thecrude product, after dried, was passed through a preparative SEC columnwith a 10% w/v THF solution (190 mL inject). The purified product wasover 97 percent pure with a molecular weight of 4490.

EXAMPLE 8 Preparation of Methacrylate-Capped Prepolymer of PolysiloxaneContaining Both Dimethylsiloxane and Phenylmethylsiloxane Having 25Percent Total Phenyl Units (2 Blocks of Silicone)

[0039] The procedure of the present example was the same as thatdescribed in Example 12 below, except a feed ratio of 3:2:2 on a molarbasis of isophorone diisocyanate, silicon of Example 7 and HEMA wasused.

EXAMPLE 9 Preparation of Methacrylate-Capped Prepolymer of PolysiloxaneContaining Both Dimethylsiloxane and Phenylmethylsiloxane Having 25Percent Total Phenyl Units (1 Block of Silicone)

[0040] The procedure of the present example was the same as thatdescribed in Example 2 above, except a feed ratio of 2:1:2 on molarbasis of isophorone diisocyanate, silicon of Example 7 and HEMA wasused.

EXAMPLE 10 Preparation of Methacrylate-Capped Prepolymer of PolysiloxaneContaining Both Dimethylsiloxane and Phenylmethylsiloxane Having 25Percent Total Phenyl Units (3 Blocks of Silicone)

[0041] The procedure of the present example was the same as thatdescribed in Example 2 above, except a feed ratio of 4:3:2 on molarbasis of isophorone diisocyanate, silicon of Example 7 and HEMA wasused.

EXAMPLE 11 Preparation of Films by Ultraviolet Light Curing of the FinalProduct of Example 2 Above (FPEx 2))

[0042] The formulations set forth in Chart 1 below also included 0.25parts benzotriazole methacrylate, 20 parts of hexanol and 1 percent2,2-dimethoxy-2-phenylacetophenone. The formulations were cured betweentwo silane-treated glass plates under an ultraviolet (UV) light sourcewith an intensity of 300 microwatts for 2 hours. The cured films werethen released, extracted in isopropanol for over 4 hours and dried in avacuum oven at 70 degrees Celsius overnight. The films withoutextractables were dried in air. All dried films were then placed in aborate buffered saline overnight before characterization. All films hada thickness of 170-200 microns. Tensile tests were performed in boratebuffered saline according to ASTM D-1708. The results are set forth inChart 1 below. CHART 1 Sample: A B C D E F G Formulation: FPEx2 65 60 6060 60 55 50 BzA 15 15 20 10 25 25 20 BzMA 15 15 10 20 5 5 10 DMA 5 10 1010 10 15 20 Properties: % 3.4 7.5 6.9 6.9 7.1 8.0 11.1 Extractables %Water 2.6 5.7 6.9 9.6 13 11.8 10.8 Modulus 1964 1791 816 1980 309 282132 g/mm² (Std. (456) (253) (56) (357) (43) (43) (3) Deviation) %Elongation 359 379 389 303 363 360 374

EXAMPLE 12 UV Curing of Formulations with a UV Filter

[0043] The formulations of the present example also include 0.25 partsbenzotriazole methacrylate, 1.0 parts bis-(2,4,6-trimethyl) benzoylphenyl phosphineoxide and 20 parts hexanol. The formulations were curedwith the same light source as that used in Example 11 above, except anUV filter was placed between the light source and the glass plates. Allprocessing conditions were the same as those of Example 11. The resultsare set forth in Chart 2 below. CHART 2 Sample: H I J K Formulation:FPEx2 100 60 0 0 FPEx4 0 0 65 0 FPEx6 0 0 0 65 BzA 0 15 15 15 BzMA 0 1515 15 DMA 0 10 5 5 Properties: % Extractables 5.0 4.8 5.5 15.1 % Water0.4 0 1.3 0.5 Modulus g/mm² 45 1209 83 2176 (Std. Deviation) (1) (203)(4) (499) % Elongation 111 355 313 320

EXAMPLE 13 Comparison of 2,2-dimethoxy-2-phenylacetophenone and Bis(2.4.6-trimethyl) Benzoyl Phenyl Phosphineoxide in UV Curing with a UVFilter

[0044] In the present example, Sample K was used except2,2-dimethoxy-2-phenylacetophenone was included in the formulationrather than bis (2,4,6-trimethyl) benzoyl phenyl phosphineoxide. Afterexposure to an UV light source for 2 hours, the formulation remainedfluid.

EXAMPLE 14 Comparison of2-benzyl-2-dimethylamino-1-(morpholinophenyl)-butan-1-one and Bis(2,4,6-trimethyl) Benzoyl Phenyl Phosphineoxide in UV Curing

[0045] In the present example, Sample K was used except2-benzyl-2-dimethylamino-1-(morpholinophenyl)-butan-1-one was includedin the formulation rather than bis (2,4,6-trimethyl) benzoyl phenylphosphineoxide. Films of the so modified Sample K had the followingproperties: 13.2% extractables; 0.5% water; 309±5% elongation and amodulus of 1841±262 g/mm².

[0046] Results from Examples 13 and 14 indicate that2,2-dimethoxy-2-phenylacetophenone does not work when the intensity oflight in the UV region is curtailed. However,2-benzyl-2-dimethylamino-1-(morpholinophenyl)-butan-1-one and bis(2,4,6-trimethyl) benzoyl phenyl phosphineoxide proved to work equallywell.

EXAMPLE 15 Curing with Blue Light as Compared to an UV Light Source

[0047] A quantity of modified Sample K of Example 14 was cured using ablue light source. The films cured using the blue light source had thefollowing properties: modulus g/mm² 1806+18 and % elongation 321±18. Theproperties were essentially the same as those of Example 14 above, whichindicates that both light sources work equally well.

EXAMPLE 16 Curing Same Formulations but with Different Prepolymers witha Blue Light Source

[0048] In the present example, the formulations set forth below in Chart3 were cured using a blue light source as described in Example 15 above.Each formulation also included 0.25 parts benzotriazole methacrylate, 1percent 2-benzyl-2-dimethylamino-1-(morpholinophenyl)-butan-1-one and 20parts hexanol. All films were processed according to the same procedureprior to characterization. CHART 3 Sample: L M N O P Formulation: FPEx250 0 0 0 0 FPEx6 0 50 0 0 0 FPEx8 0 0 50 0 0 FPEx9 0 0 0 50 0 FPEx10 0 00 0 50 BzA 20 20 20 20 20 BzMA 10 10 10 10 10 DMA 20 20 20 20 20Properties: % Extractables 15.6 14.4 11.6 8.4 13.1 % Water 11.7 10.5 7.8Modulus, g/mm² 94 131 108 279 115 (Std. Deviation) (8) (41) (7) (26) (9)% Elongation 438 415 346 222 290

EXAMPLE 17 Curing Low Water and no Water Formulations Using a Blue LightSource

[0049] In the present example, the formulations set forth below in Chart4 were cured using a blue light source as described in Example 15 above.Each formulation also included 0.25 parts benzotriazole monomer, 1percent 2-benzyl-2-dimethylamino-1-(morpholinophenyl)-butan-1-one and 20parts hexanol. All films were processed according to the same procedureprior to characterization. CHART 4 Sample: Q R S T U V Formulation:FPEx2 90 0 0 0 0 0 FPEx4 0 90 0 0 0 0 FPEx6 0 0 90 0 0 0 FPEx8 0 0 0 9085 85 BzA 0 0 0 0 5 0 BzMA 5 5 5 5 5 10 DMA 5 5 5 5 5 5 Properties: %Extractables 17.1 9.7 12.0 13.6 12.8 13.4 % Water 3.0 4.4 2.1 2.3 0.3 0Modulus, g/mm² 69 81 81 63 62 104 (Std. Deviation) (1) (4) (4) (4) (15)(9) % Elongation 134 137 132 213 127 203

EXAMPLE 18 Cast Molding of Formulations

[0050] In the present example, a quantity of Sample K from Example 12above and a quantity of Sample P from Example 16 above were cast moldedbetween two plastic molds under a UV light source to produce IOLs. Thesubject IOLs were extracted with isopropanol and proved to have goodclarity.

[0051] Medical devices produced using the polymeric compositions of thepresent invention may be manufactured in accordance with methods knownto those skilled in the art of the specific ophthalmic device beingproduced. For example, if an intraocular lens is to be produced, thesame may be manufactured by methods known to those skilled in the art ofintraocular lens production.

[0052] Ophthalmic devices such as but not limited to IOLs and cornealinlays manufactured using the polymeric compositions of the presentinvention can be of any design capable of being rolled or folded forimplantation through a relatively small surgical incision, i.e., 3.5 mmor less. For example, intraocular implants such as IOLs comprise anoptic portion and one or more haptic portions. The optic portionreflects light onto the retina and the permanently attached hapticportions hold the optic portion in proper alignment within an eye. Thehaptic portions may be integrally formed with the optic portion in aone-piece design or attached by staking, adhesives or other methodsknown to those skilled in the art in a multipiece design.

[0053] The subject ophthalmic devices, such as for example IOLs, may bemanufactured to have an optic portion and haptic portions made of thesame or differing materials. Preferably, in accordance with the presentinvention, both the optic portion and the haptic portions of the IOLsare made of the same polymeric composition of the present invention.Alternatively however, the IOL optic portion and haptic portions may bemanufactured from different materials and/or different formulations ofthe polymeric compositions of the present invention, such as describedin detail in U.S. Pat. Nos. 5,217,491 and 5,326,506, each incorporatedherein in their entirety by reference. Once the material(s) areselected, the same may be cast in molds of the desired shape or cast inthe form of rods and lathed or machined into disks. If cast in the formof rods and lathed or machined into disks, the disks may then be lathedor machined at a relatively low temperature below that of the glasstransition temperature of the material(s) to produce IOLs. The IOLswhether molded or machined are then cleaned, polished, packaged andsterilized by customary methods known to those skilled in the art.

[0054] In addition to IOLs, the polymeric compositions of the presentinvention are also suitable for use in the production of otherophthalmic devices such as contact lenses, keratoprostheses, capsularbag extension rings, corneal inlays, corneal rings and like devices.

[0055] Ophthalmic devices manufactured using the unique polymericcompositions from the unique prepolymers and prepolymer precursors ofthe present invention are used as customary in the field ofophthalmology. For example, in a surgical cataract procedure, anincision is placed in the cornea of an eye. Through the corneal incisionthe cataractous natural lens of the eye is removed (aphakic application)and an IOL is inserted into the anterior chamber, posterior chamber orlens capsule of the eye prior to closing the incision. However, thesubject ophthalmic devices may likewise be used in accordance with othersurgical procedures known to those skilled in the field ofophthalmology.

[0056] While there is shown and described herein certain prepolymers,polymeric compositions, methods of producing the prepolymers andpolymeric compositions and ophthalmic devices made from the subjectprepolymers and polymeric compositions in accordance with the presentinvention. Likewise, it will be manifest to those skilled in the artthat various modifications may be made without departing from the spiritand scope of the underlying inventive concept and that the same is notlimited to particular structures herein shown and described exceptinsofar as indicated by the scope of the appended claims.

We claim:
 1. A prepolymer comprising:

wherein the V groups may be the same or different unsaturated photo orthermal polymerizable substituents of the general structureR₃CH═C(R₄)(CH₂)_(p)(W)_(q)(Z)_(q)(Ar)_(q)R₅; the R groups may be thesame or different saturated C₁₋₁₀ hydrocarbon substituents; the R₁groups may be the same or different C₁₋₁₀ alkyl substituents; the R₂groups may be the same or different selected from the group consistingof C₁₋₁₀ alkyl substituents, C₁₋₁₀fluoroalkyl substituents, C₂₋₂₀alkyl-fluoroalkyl substituents and C₆₋₃₀ aromatic substituents such asfor example but not limited to phenyl; the L groups, which may or maynot be present in the subject prepolymers, may be the same or differenturethane, urea, carbonate or ester linkages; y is a natural numbergreater than 4 representing the sum of siloxane moieties with randomlydiffering R₂ groups as defined above so as to have a molar ratio ofaromatic substituents to alkyl substituents no less than 1:4; x is anatural number such that the prepolymer molecular weight is at leastapproximately 1000 and refractive index is at least approximately 1.45;R₃ is selected from the group consisting of hydrogen, C₁₋₁₀alkyl and—CO—U—R₁, but preferably hydrogen; R₄ is selected from the groupconsisting of hydrogen and methyl; R₅ is a C₁₋₁₀ divalent alkyleneradical; the W group is selected from the group consisting of —CO— and—OCO—; the Z group is selected from the group consisting of —O— and—NH—; the Ar groups may be the same or different C₆₋₃₀ aromaticradicals; p is a non-negative integer less than 7; q is either 0 or 1;and U is selected from the group consisting of —OC₁₋₁₂ alkyl radical,—SC₁₋₁₂ alkyl radical and —NHC₁₋₁₂ alkyl radical.
 2. The prepolymer ofclaim 1 wherein at least one of said V groups is an acrylate group. 3.The prepolymer of claim 1 wherein at least one of said V groups is amethacrylate group.
 4. The prepolymer of claim 1 wherein at least one ofsaid L groups is a urethane linkage.
 5. The prepolymer of claim 1wherein each R₁ group is methyl and each R₂ group is phenyl.
 6. Theprepolymer of claim 1 wherein each R group is trimethylene ortetramethylene.
 7. A polymeric composition produced through thecopolymerization of one or more prepolymers of claim 1 with one or morearomatic monomers, alkyl monomers, hydrophilic monomers or a combinationthereof.
 8. The polymeric composition of claim 7 wherein said one ormore aromatic monomers are selected from the group consisting ofacrylates, methacrylates, acrylamides and methacrylamides, each witharomatic substituents.
 9. The polymeric composition of claim 7 whereinsaid one or more aromatic monomers are selected from the groupconsisting of phenyl acrylate, phenyl(meth)acrylate, phenyl acrylamide,benzyl acrylate, benzyl acrylamide, phenylethylacrylate,phenyl(meth)acrylamide, phenylethyl(meth)acrylate andbenzyl(meth)acrylate.
 10. The polymeric composition of claim 7 whereinsaid one or more alkyl monomers are selected from the group consistingof C₁₋₂₀ alkyl acrylate, C₁₋₂₀ alkyl methacrylate, C₅₋₂₀ acrylamide andC₅₋₂₀ methacrylamide.
 11. The polymeric composition of claim 7 whereinsaid one or more alkyl monomers are selected from the group consistingof methyl acrylate, ethyl acrylate, n-propyl acrylate, n-butyl acrylate,n-hexyl acrylate, n-octyl acrylate, 2-ethylhexyl acrylate, n-propylmethacrylate, n-butyl methacrylate, n-hexyl methacrylate, n-octylmethacrylate, 2-ethylhexyl methacrylate and n-octyl acrylamide.
 12. Thepolymeric composition of claim 7 wherein said one or more hydrophilicmonomers are selected from the group consisting of N,N-dimethylacrylamide, N-vinylpyrrolidone, 2-hydroxyethyl methacrylate, glycerolmethacrylate, 2-hydroxyethyl acrylate, acrylamide, n-methyl acrylamide,acrylic acid and (meth)acrylic acid.
 13. A method of manufacturing theprepolymer of claim 1 comprising: reacting a hydroxyalkyl-terminatedpolysiloxane with a diisocyanate, a diacidchloride or phosgene; andend-capping with a hydroxy or amino containing monomer.
 14. The methodof claim 13 wherein said diisocyanate is isophorone diisocyanate.
 15. Amethod of producing the polymeric composition of claim 7 useful in themanufacture of ophthalmic devices comprising: reacting one or morepolysiloxane prepolymers with one or more aromatic monomers, alkylmonomers or hydrophilic monomers.
 16. The method of claim 15 whereinsaid one or more aromatic monomers are selected from the groupconsisting of acrylates, methacrylates, acrylamides and methacrylamides,each with aromatic substituents.
 17. The method of claim 15 wherein saidone or more aromatic monomers are selected from the group consisting ofphenyl acrylate, phenyl(meth)acrylate, phenyl acrylamide, benzylacrylate, benzyl acrylamide, phenylethylacrylate,phenyl(meth)acrylamide, phenylethyl(meth)acrylate andbenzyl(meth)acrylate.
 18. The method of claim 15 wherein said one ormore alkyl monomers are selected from the group consisting of C₁₋₂₀alkyl acrylate, C₁₋₂₀ alkyl methacrylate, C₅₋₂₀ acrylamide and C₅₋₂₀methacrylamide.
 19. The method of claim 15 wherein said one or morealkyl monomers are selected from the group consisting of methylacrylate, ethyl acrylate, n-propyl acrylate, n-butyl acrylate, n-hexylacrylate, n-octyl acrylate, 2-ethylhexyl acrylate, n-propylmethacrylate, n-butyl methacrylate, n-hexyl methacrylate, n-octylmethacrylate, 2-ethylhexyl methacrylate and n-octyl acrylamide.
 20. Themethod of claim 15 wherein said one or more hydrophilic monomers areselected from the group consisting of N,N-dimethyl acrylamide,N-vinylpyrrolidone, 2-hydroxyethyl methacrylate, glycerol methacrylate,2-hydroxyethyl acrylate, acrylamide, n-methyl acrylamide, acrylic acidand (meth)acrylic acid.
 21. A method of producing an ophthalmic deviceusing the polymeric composition produced through the method of claim 15comprising: casting said polymeric composition in the form of a rod;lathing or machining said rod into disks; and lathing or machining saiddisks into an ophthalmic device.
 22. A method of using the ophthalmicdevice produced through the method of claim 21 comprising: making anincision in the cornea of an eye; and implanting said ophthalmic device.23. A method of producing an ophthalmic device using a polymericcomposition produced from one or more of the prepolymers of claim 1comprising: pouring said polymeric composition prior to curing into amold; curing said polymeric composition; and removing said polymericcomposition from said mold following curing thereof.
 24. A method ofusing the ophthalmic device produced through the method of claim 21 or23 comprising: making an incision in the cornea of an eye; andimplanting said ophthalmic device.
 25. A prepolymer comprising:

wherein IPDI represents an isophorone diioscyanate residue afterremoving an isocyanate group, the Ph groups are the same or differentaromatic substituents and x is a natural number such that the prepolymermolecular weight is at least approximately 1000 and refractive index isat least approximately 1.45.